biojuice

The WSJ reports that Genentech is restricting the availability of Avastin to compounding pharmacies in an effort to prevent the re-formulation and use of Avastin to treat wet macular degeneration. Irv Arons has written a fascinating series of posts about the Avastin/Lucentis debate.

Lucentis is derived from Avastin, but they are different molecules and not just different formulations of the same drug. Lucentis (Ranibizumab) is a 48kD protein consisting of a humanized Fab fragment; Avastin (Bevacizumab) is an 148kD IgG1 antibody. It’s not at all obvious that they’re going to work exactly the same when injected into an eye, and the clinical trials comparing them are still ongoing.
That a significant number (50%?) of patients and doctors are willing to potentially compromise suggests that the Lucentis price is way too high (at least for some patients) given its advantages, perceived or otherwise. Presumably there is some point at which the benefits of a molecule and formulation optimized for the eye is worth some extra expense if it works better. On the other hand, using Avastin is apparently effective, widely used, and seems to be safe, based on a grass-roots safety monitoring study, the International Intravitreal Bevacizumab (Avastin) Safety Survey.

It seems clear that there is some price-gouging going on, but there are also legitimate reasons to prefer Lucentis, and the safety concerns are logical, even if they may be overstated. I wonder whether there is any possibility for a company to be held liable for problems resulting from off-label use of a drug — if so, that does partially justify taking steps to discourage off-label uses.

What if the original producers of clinical trial data - the patients - could seize ownership of their own clinical data, and then publish and redistribute it as they saw appropriate? Or equivalently, if patients demanded transparency of primary data (hopefully in collusion with their doctors) as a precondition to consenting to become clinical subjects?

It’s analogous to users taking ownership and exerting control over their clickstream and attention data…

Great editorial by Donald Kennedy in Science this week about improving US drug regulation:

“The pharmaceutical business is a multinational enterprise of great significance to human health. The U.S. Food and Drug Administration (FDA), once called the world standard in regulating new drug approvals, may still deserve that status. But, as was described earlier in this space, public confidence in the agency has been shaken. That’s why it’s important that we restore the FDA’s capacity to do the quality of work that all health care systems require.

…

With respect to the last of these, the problem is that the United States lacks a system that is adequately tuned to detect adverse reactions. That measure requires a numerator and a denominator: the number of reported adverse events divided by the number of prescriptions issued. The FDA knows neither. Event reporting is voluntary, yielding a record of dubious reliability, and there’s no national prescription record. That’s why the FDA had to use Kaiser, a large health maintenance organization, to find an adequate database for evaluating the safety of Vioxx. Information about all clinical trials reviewed by the FDA should be made publicly available at the FDA’s Web site and also be linked to the National Institutes of Health’s Web site, ClinicalTrials.gov. Why? Recently, a Cleveland Clinic cardiologist analyzed trials conducted on GlaxoSmithKline’s diabetic drug Avandia. His meta-analysis revealed cardiovascular risks that had been hinted at in earlier published trials but were not statistically significant in any one trial. The study, published in the New England Journal of Medicine, illustrates the difficulty of finding important trial data. The journal has since been attacked by the company, some physicians, and an unfortunate editorial in the Lancet, but it deserves praise instead.”

The Times had another good article last month about this issue with respect to Avandia:

For Drug-makers, A Downside to Full Disclosure

Nice article by Adam Feuerstein over at TheStreet.com suggesting that leaked ASCO abstracts have been moving stocks including Imclone [IMCL], Genentech [DNA], Regeneron [REGN], and Onyx [ONXX].

Of course, this wouldn’t be the first time.

Why can’t they just publish everything on the web and make it available to everyone simultaneously?

The unstoppable trend towards consolidation of protein therapeutic and antibody companies by big pharma continues. Today saw the $325M acquition of privately-held Morphotek of Exton, PA by Eisai of Tokyo. Morphotek uses human B-cell hybridomas to make fully human monoclonals, which they optimize with morphogenics, their technology to create hypermutable hybridoma libraries by disabling DNA mismatch repair processes [pubmed]. Morphotek has a number of antibodies in clinical development, mainly in oncology.

Some other representative transactions in biologics:

• Avidia, by Amgen for ~$290M+ (Sept 2006)
• Abgenix by Amgen for ~$2.2B (Dec 2005)
• Cambridge Antibody Technology by AstraZeneca for £702M (May 2006)
• GlycFi for $400M and AbMaxis for $80M by Merck (May 2006)

Public companies in the biologics space to keep an eye on include:

Seattle Genetics [SGEN], Medarex [MEDX], and Regeneron [REGN]

A few IPOs happening and lined up:

Oculus Innovative Sciences [OCLS] priced today at $8 and raised about $24 million. Oculus makes “a pH-neutral, super-oxidized water that contains “oxidizing species” generated by the electrolysis of sodium chloride and water” used for wound care. [S-1] Bottled water is big business…

Rehovot-based Rosetta Genomics, is developing therapeutics and diagnostics based on MicroRNAs, and filed to raise about $32 mil. More on Rosetta at SeekingAlpha and on the F-1. Couldn’t they have come up with a more original name than Rosetta?

Also on deck: Synta, Molecular Insight, and CardioMEMS.

Pfizer Inc., the world’s largest pharmaceuticals maker, and Merck & Co. may buy biotech companies to make up for a scarcity of experimental medicines and expiring patents for best-selling products. On the shopping list are companies with experimental compounds as well as those with new drug-development science and technologies, investors at the conference said.

Bloomberg: Drugmakers’ `Arms Race’ May Spur Biotech Deals in 2007